This invention relates to photosensitive caged molecules, e.g., photosensitive caged peptides.
The development of therapeutic drugs, in general, involves screening natural products or synthetic compounds for substances that affect or interfere with biological processes associated with disease. This random approach was required, in part, by limited knowledge concerning the molecular aspects of such disease processes. Development of molecular genetic techniques has led to the identification of key molecules, e.g., peptides and other small molecules, that regulate normal biological processes, and, in some situations, has defined the cellular pathways responsible for disease. Accordingly, this information can now be exploited and manipulated for the rational design of therapeutic drugs or diagnostic/research agents that specifically target these pathways.
The activity of such molecules can be further controlled and regulated in a specific manner by designing molecules whose biological activity is controlled by light. Such molecules are generally referred to as being "caged." The term caged is utilized as an indication that a biologically active species is trapped inside a larger framework that would be released upon illumination, thus "uncaging" the contents (Adams et al., Annu. Rev. Physiol. 55: 755-784, 1993).
For example, attempts have been made to control the activity of biologically active macromolecules, e.g., peptides, using caging chemistry. Initial efforts, however, to modify peptides selectively on amino acid side chains with photolabile protecting groups, have met with only limited success (Adams et al., supra). This is due, in part, to a lack of specificity for a photolabile caging group to specific amino acid residues in the peptide.